There is no currently available method to unambiguously and rapidly determine whether a person is actively infected with Mycobacterium tuberculosis or isoniazid resistant Mycobacterium tuberculosis. Skin tuberculin testing with purified protein derivative (PPD), is a useful first screen for potential exposure to mycobacteria but does not differentiate between prior exposure or currently active infection; chest X-rays only identify advanced lung lesions; a smear test is highly reliable but of low sensitivity since many TB patients do not present as smear positive; sputum culture of slow-growing TB bacteria is a definitive test but takes a long time and only detects active disease. This lack of an optimal test is a long-felt need with important implications. One of the most important aspects is that an improved test which will allow vaccination against TB using the BCG vaccine without impairing the ability of the diagnostic test to reliably predict the existence of TB infection despite vaccination, would make vaccination with BCG a viable choice for healthcare consumers who wish to make informed healthcare decisions. Moreover, by no longer relying upon current tuberculin testing, the benefits of BCG vaccination could be used in certain populations (e,g. troops and related personnel at risk of TB infection in areas with high incidence of TB). But since TB may become more widespread, and has potential for bioterror use, general use for the US population might also be an option. Another important aspect is that diagnosis of active TB can be made rapidly at a point of care, so that treatment can begin immediately, and so can help prevent further spread of the disease compared to diagnostic modalities that require long waiting periods between sampling and diagnosis.